The proposed studies are part of a continuing effort by this laboratory to evaluate the potential for synaptic plasticity in the motor thalamus as well as to determine the long-term effects of lesions in the basal ganglia output structures (substantia nigra pars reticularis, SNr, and entopeduncular nucleus, EPN) on thalamic GABA receptors. Specific aims of this proposal are to determine long-term (11 and 17 months survival) changes in a) synaptic organization, and b) binding parameters of two GABA/A receptor ligands (3H- muscimol and 3H-flunitrazepam) in the thalamus induced by lesioning of basal ganglia output structures. Specifically these changes will be determined in the ventral anterior, ventral medial and ventral lateral thalamic nuclei after 3 different combinations of lesions (SNr, EPN, and SNr + EPN). The techniques to be used in these studies include stereotactic surgery that employs an intracerebral coordinate system and contrast ventriculography, quantitative receptor binding autoradiography with computer-assisted image analysis, and quantitative ultrastructral analysis aided by computer software for processing of large files containing morphometric data. The proposed studies will provide information for (1) further understanding the functional role of the basal ganglia in the motor control, (2) evaluating the possible contribution of synaptic remodeling in the thalamus to the pathogenesis of dyskinetic disorders, and (3) understanding the mechanism of lesion-induced changes in the GABA receptors and their relevance to clinical conditions caused by impairment of functioning of the basal ganglia.